Potential risk of poisoning by nerve agent Injury, Occupational Diseases, Poisoning
Conditions
Interventions
Generic drug name- physostigmine and hyoscine (transdermal patch)
Dosage - period 1: a single 72 hour application of active 25cm2 patch formulation F-11.
Dosage – peri
Sponsors
Defence Science and Technology Laboratory
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Ability to give written informed consent prior to study participation 2. Healthy Caucasian male participants aged between 18 and 45 years (inclusive) 3. Body Mass Index (BMI) within the range of = 21 and = 30 kg/m2 4. Vital signs within the following ranges: 4.1. Pulse rate 40-90 bpm 4.2. Systolic blood pressure 90-140 mmHg 4.3. Diastolic blood pressure 50-90 mmHg 5. Ability to communicate well with the Investigator and to comply with the requirements of the study.
Exclusion criteria
Exclusion criteria: Screening: 1. Presence of any clinically-significant medical condition as determined by the investigator 2. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug (e.g. renal or liver disease, respiratory, immunological, endocrine or neurological disorders) 3. Any ECG abnormality other than sinus bradycardia or respiratory sinus arrhythmia 4. Known or suspected hypersensitivity or idiosyncratic reaction related to any of the study products 5. Any history of contact dermatitis 6. A dibucaine number of less than 70 7. Any skin disorder, broken skin, scars, tattoos at the sites of patch application (i.e. on both arms) 8. Glaucoma or a history of glaucoma in first-degree relatives (i.e. parents, siblings or offspring) 9. Presence of Anterior Chamber Narrow Angle (Van Herrick Grade 1 and 2) 10. Intra-ocular pressure exceeding 20 mm Hg 11. Uncorrected vision in both eyes of worse than 6/9 on the Snellen Scale 12. Corrected vision of 6/9 or better on the Snellen Scale when wearing +2.25 dioptre reading glasses 13. Requires glasses or contact lenses for distance vision 14. History of asthma (within the previous 10 years), exercise-induced bronchospasm or relevant seasonal bronchospasm 15. Lung function of less than 80% of predicted FEV1 and FVC values 16. History or evidence of drug abuse (opiates, methadone, cocaine, amphetamines, methamphetamines, cannabinoids, barbiturates) 17. Positive test for HIV, Hepatitis B surface antigen or Hepatitis C antibody 18. History or evidence of alcohol abuse defined as an intake of more than 28 units per week (where 1 unit corresponds to 250 ml beer, 20 ml spirits/liqueur or one glass (100 ml) of wine) 19. Positive urine test for alcohol 20. Participation in another clinical study within the last three months 21. Use of any prescription medication within the last 14 days 22. Use of non-prescription medication within the last 7 days (apart from paracetamol) 23. Donation of blood or blood products within the last 3 months, or the intention to donate blood or blood products within 3 months after completion of the study Baseline: 1. Development of any exclusion criteria since screening 2. Positive urine test for alcohol 3. Positive drugs of abuse test 4. Use of any prescription medication since screening 5. Use of non-prescription medication may impact the safety aspects and objectives of the study, within the last 7 days (apart from paracetamol)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of the drug assessed by monitoring vital signs, ECG, ocular function (near point), patch application site assessment, using digital photography. Tests were performed at intervals for up to Day 14 in period 1 and Day 20 in period 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic (PK) and pharmacodynamic (PD) profiles measured at regular time points at pre-dose and up to 96 hours after patch application 1.1. Physostigmine and hyoscine plasma measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS) method 1.2. Acetylcholinesterase levels measured at baseline, pre-dose, and intervals up to 96 hours after patch application. The method was validated spectrophotometric method | — |
Countries
United Kingdom
Outcome results
None listed